In vivo evaluation of intravesical paclitaxel and combined bcl-xL antisense oligodeoxynucleotide treatment for orthotopic urothelial carcinoma.
OBJECTIVE
To evaluate intravesical paclitaxel monotherapy and combined treatment with antiapoptotic bcl-xL antisense oligodeoxynucleotides (AS-ODNs) on urothelial carcinoma (UC).


METHODS
Forty-eight FoxN(rnu) athymic nude rats with orthotopic human bladder UC were randomized to four treatment groups [1, paclitaxel; 2, paclitaxel/bcl-xL AS-ODNs; 3, bcl-xL AS-ODNs (control); 4, medium (control)]. Three consecutive instillations were applied and weekly endoscopic tumor size measurements were performed.


RESULTS
Significant tumor size reduction was achieved in groups 1 and 2 (each P < 0.0001), whereas continuous UC growth was observed in control animals (groups 3 and 4; P < 0.0001 and P < 0.0020). Complete tumor eradication was achieved in four treated animals (groups 1 and 2). No significant difference in chemoresection effects was found between groups 1 and 2 (P = 0.2251).


CONCLUSIONS
We present an in vivo evaluation of intravesical treatment with paclitaxel and combined bcl-xL AS-ODNs. Despite efficient tumor size reduction, no gain was observed when adding bcl-xL AS-ODNs in this experimental setting.
Bolenz
Christian
C
Department of Urology, Mannheim Medical Center, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, Mannheim, Germany. christian.bolenz@uro.ma.uni-heidelberg.de
Weiss
Christel
C
Wenzel
Melanie
M
Gabriel
Ute
U
Steidler
Annette
A
Becker
Andreas
A
Herrmann
Edwin
E
Trojan
Lutz
L
Michel
Maurice Stephan
MS
D000283:Administration, Intravesical; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000627:therapeutic use*; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D011923:Rats, Nude; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051020:bcl-X Protein / Q000235:genetics*
D000972:Antineoplastic Agents, Phytogenic; C494813:Bcl2l1 protein, rat; D016376:Oligonucleotides, Antisense; D051020:bcl-X Protein; D017239:Paclitaxel